Nanodiamonds have numerous useful properties, ranging from lubrication, to nanofillers for polymer and metal composites, and to medical applications. Nanodiamonds produced through a detonation process are biocompatible, inexpensive to produce, and scalable. Recently, progress in preparing aqueous dispersions of nanodiamonds has facilitated their use both in biomedical field and in polymer composites.
Many existing and potential applications in the biomedical and pharmaceutical fields, in particular, depend upon nanodiamonds having a very small average particle size. For example, nanoparticles having a particle size within the range of 10-100 nanometers can be suspended and circulate within blood, and are readily removed from the bloodstream by the kidneys. Nanoparticles smaller than 10 nanometers have several additional properties, such as the ability to penetrate the blood-brain barrier or a cell's nuclear pore complex, that are highly desirable in biomedical applications.
Unfortunately, nanodiamonds have a strong tendency to aggregate, forming strongly-bound aggregates comprising 10, 20, or even 100 or more primary nanodiamond particles. Detonation nanodiamond particles, in particular, are known to form aggregates that cannot be destroyed by traditional means such as sonication or milling. It is therefore highly desirable to develop methods of disaggregating nanodiamond clusters and obtaining single-digit nanodiamonds (i.e., single digit nanodiamonds having a diameter of smaller than 10 nanometers).
Several disaggregation methods for nanodiamond suspensions are known in the art, including ball milling, attrition milling, and bead-assisted sonic disintegration (BASD). Each of these techniques can be used to obtain single-digit nanodiamond suspensions. Unfortunately, each of the known disaggregation techniques possesses one or more significant disadvantages. For example, many known disaggregation techniques introduce impurities into the nanodiamond material, which presents a significant concern in the biomedical context. In addition, many known disaggregation methods are complex, require expensive custom-made equipment, and/or significantly increase the cost of obtaining single-digit nanodiamonds.
Recently, U.S. Patent Application Publication No. 2015/0038593, which is herein incorporated by reference, disclosed a dry media-assisted attrition milling process that utilized crystalline milling media, such as sodium chloride or sucrose, to disaggregate nanodiamond clusters. This process provided several significant improvements relative to previously known wet milling processes, which had required the use of zirconia as the milling media.
Unfortunately, the process disclosed in the '593 publication still presents a number of drawbacks that limit its usefulness in preparing disaggregated nanodiamonds for biomedical applications. In addition to being relatively expensive and costly to maintain, attrition mills use steel jars, shafts and balls, which represent sources of metal contaminants and are subjected to severe wear and corrosion during the milling process, especially in the presence of salt. As a result, nanodiamonds produced using the process described in the '593 publication are often contaminated with metal impurities, including iron and other components of the steel. While many of the metal impurities are soluble in acids, they require the use of an additional purification step that reduces the overall efficiency and adds to the cost and complexity of the process. Additionally, while the process described in the '593 publication can reduce the size of the nanodiamond aggregates down to an average diameter of 30-50 nanometers, single-digit nanodiamonds cannot be obtained unless the dispersion pH is adjusted to approximately 11 upon completion of the milling. This requires the introduction of yet another process step, and adds still more cost and complexity.
It is therefore highly desirable to develop a method for disaggregating nanodiamonds that is inexpensive, easy to implement, and does not introduce unwanted impurities into the nanodiamond material.